This proposal presents a collaboration between laboratories in two academic institutions (Johns Hopkins University and Kennedy Krieger Institute) with complementary capabilities and resources to deliver a state of the art technology for simultaneous optogenetic control of neuronal activity and functional imaging in awake, behaving animals. We propose to deliver within two years a head-mountable, multifunction, tether-free optical system - a novel microscope - capable of remotely controlling genetically targeted neurons and imaging functional blood flow response in free-moving rats. Highly innovative aspects of this proposal are the miniaturized head-mountable optical microscope for light delivery for optogenetic control and a unique, customized very large scale integrated (VLSI) circuit chip for functional imaging using the method of laser speckle contrast imaging (LSCI). A behavioral study on rat whisker involvement in texture discrimination will be carried out to explore how inactivation of the interested barrel cortex fields affects functional responses of cerebral blood flow and how it is translates into explicit behavior. Preliminary work done for this revised application has resulted in a prototype with size and weight compatible for mounting the microscope on awake and undeterred rodents, as well as optics producing artifact free image quality comparable to bench top systems. Changes in blood flow due to optical stimulation by halorhodopsin activation have also been imaged for the first time. The high impact of this work stems from the potential to do functional neuroscience research in awake and behaving animals and thereby addressing one of the biggest limitations of requiring restraint and anesthesia. This technology will open the door for new fundamental research on manipulating neuronal circuits, neurovascular coupling, functional and structural changes during development, and learning and plasticity during natural behavior as well as in models of stroke, migraine or seizure. PUBLIC HEALTH RELEVANCE: A novel head-mounted microscope for simultaneous optogenetic control of neuronal activity and functional imaging in awake, behaving animals is proposed. This approach is made possible by a miniature head mounted system for light delivery and imaging with a novel integrated circuit imager chip. As a proof of concept, optogenetic control of neuronal activity in freely moving rats involved in behavioral study of texture discrimination will be carried out and images of cerebral blood flow in the barrel cortex fields will be obtained by the head-mounted microscope.